title: Enhanced inducible costimulator ligand (ICOS-L) expression on dendritic cells in interleukin-10 deficiency and its impact on T-cell subsets in respiratory tract infection.
abstract: An association between inducible costimulator ligand (ICOS-L) expression and interleukin (IL)-10 production by dendritic cells (DCs) has been commonly found in infectious disease. DCs with higher ICOS-L expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Tregs). Here we use the Chlamydia muridarum (Cm) lung infection model in IL-10 knockout (KO) mice to test the relationship between IL-10 production and ICOS-L expression by DCs. We examined ICOS-L expression, the development of T-cell subsets, including Treg, Th17 and Th1 cell, in the background of IL-10 deficiency and its relationship with ICOS-L/ICOS signaling after infection. Surprisingly, we found that the IL-10 KO mice exhibited significantly higher ICOS-L expression by DCs. Moreover, IL-10 KO mice showed lower Tregs but higher Th17 and Th1 responses, but only the Th17 response depended on ICOS signaling. Consistently, most of the Th17 cells were ICOS⁺, whereas most of the Th1 cells were ICOS⁻ in the infected mice. Furthermore, neutralization of IL-17 in IL-10 KO mice significantly exacerbated lung infection. The data suggest that ICOS-L expression on DC may be negatively regulated by IL-10 and that ICOS-L expression on DC in the presence or absence of IL-10 costimulation may promote Treg or Th17 response, without significant impact on Th1.
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Gao
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Shuhe
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory for Infection and Immunity, Departments of Medical Microbiology and Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D060945:Inducible T-Cell Co-Stimulator Ligand / Q000235:genetics / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D020381:Interleukin-17 / Q000037:antagonists & inhibitors; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: C508609:IL10 protein, human; D060945:Inducible T-Cell Co-Stimulator Ligand; D020381:Interleukin-17; D016753:Interleukin-10